The HIV retrovirus is the etiologic agent for AIDS. The tat (trans-activating transcriptional) protein encoded by HIV has the ability to autoregulate the expression of HIV by promoting the transcriptional activity of the HIV LTR promoter. The molecular cloning of HIV has provided the isolation of tat coding DNA from other HIV coding sequences and has facilitated studies of the protein activity independent of other retroviral proteins. We are studying the transcriptional activity of the tat protein on the HIV LTR promoter and on other constitutively expressed cellular genes. The effect of the tat genes and proteins on tissue specific expression as well as the role of cellular proteins on tat activity are being examined using model systems based on human continuous cell lines, such as the K562 erythroleukemia cell line which expresses specific globin genes. Both structural and functional assays are being used to characterize the transcriptional activity of the tat gene and protein. Large scale production, isolation, and purification, of the tat protein from prokaryotic and eukaryotic cells, using cloned tat DNA in suitable expression vectors, is being done to be able to study structure- function relations (by protein chemical methods including NMR and X-ray crystallography) and to develop assays for the study of potential inhibitors of the protein. This work could lead to a new approach to the prevention or treatment of AIDS.